tbuckley/cabot-search huggingface dataset:
Abstract 14879: Circadian Variation in Pre-Procedural Rupture of Acute Type A Aortic Dissection
Authors: chen lu, JIA HU
Journal: Circulation (2022)

Introduction: Acute type A aortic dissection (ATAAD) is a devasting cardiovascular disease. Though it is recommended by guidelines, urgent open surgery was not accessible for all patients. Transferring patients to comprehensive aortic centers, inadequate medical assistance in low-resource health systems or financial issues would delay the timing of surgery. There have been several reports about the connection between circadian variation and cardiovascular disease. The study was conducted to examine the circadian variation in pre-procedural rupture of ATAAD in the hospital. Methods: The study enrolled ATAAD patients who died from aortic rupture within 7 days since onset in our center from January 2010 to December 2020. Patients who died within 1 hour after admission were excluded. All patients accepted anti-impulse therapy immediately upon admission. Clinical data were retrospectively collected from medical records. Results: In total, 200 ATAAD patients were enrolled in the retrospective observational study. Mean age of recruiters was 55.98 ± 11.82 years and 159 (78.5%) were men. Mean time from onset to admission was 26.78 ± 24.97 hours and mean time from onset to rupture was 48.27 ± 42.01 hours. Distributions of rupture time were visualized through histogram. The peaks of the occurrence of aortic rupture were in 6:00-8:00 (26%) and 18:00-22:00 (36%). Kernel density estimation was consistent with the results. Conclusions: Rupture of ATAAD does not seem to be a random phenomenon, while the peak of occurrence was consistent with the circadian rhythm. Even when the hemodynamic state was well controlled, fluctuant blood pressure and heart rate that influenced by the circadian rhythm would increase the risk of aortic rupture. During 6:00-8:00 and 18:00-22:00, more frequent blood pressure measurement and does adjustment of intravenous anti-impulse drugs might improve aortic rupture reduction. What’s more, bedtime hypertension treatment might also help.
Abstract 15694: Mitochondrial Dysfunction and Fatty Acid Metabolism Derangement in Pediatric Single Ventricle Congenital Heart Disease
Authors: Tahmina Samad, Francisco X Galdos, Sharon Paige, Soah Lee, Daniel Lee, Paul Heinrich, Sean M Wu
Journal: Circulation (2022)

Introduction: Cardiac dysfunction is a common complication in pediatric patients with single ventricle (SV) physiology. While many factors contribute to the development of SV heart failure (HF), metabolic switch from fatty acid utilization to carbohydrate metabolism has been shown to contribute to cardiac dysfunction in adult HF. Hypothesis: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from pediatric SV HF patients exhibit reduced fatty acid utilization and decreased contractility when compared with hiPSC-CMs from healthy control individuals. Methods: We differentiated iPSCs from pediatric patients with hypoplastic left heart syndrome (HLHS) who developed early onset HF and from healthy control individuals to generate hiPSC-CMs. We plated hiPSC-CMs on hydrogel micropattern for single-cell plating and measured their contractile phenotype using the Sony SI8000 cell motion imaging system. We used Seahorse XF assay to measure metabolism in hiPSC-CMs. Furthermore, we performed metabolomic profiling of day 20 and day 45 hiPSC-CMs. Results: HLHS hiPSC-CMs demonstrated metabolic derangement with significant reduction in ATP production (p &lt;0.001) and in basal and maximal respiration (p &lt;.001). We also found that HLHS hiPSC-CMs have impaired contractility when compared to WT hiPSC-CMs. Contraction force and acceleration were decreased on HLHS hiPSC-CMs compared to WT hiPSC-CMs (p&lt;0.01). Our metabolomic profiling identified a reduction of tricarboxylic acid (TCA) cycle metabolites such as succinyl carnitine (p = 0.002) and alpha-ketoglutarate (p = 0.056) in HLHS cells compared to healthy controls at day 20 and day 45 of differentiation. In addition, succinate, fumarate, malate, itaconate and citraconate/ glutaconate were also significantly reduced in day 20 media of HLHS hiPSC-CMs and trended lower in day 45 HLHS hiPSC-CMs. Conclusions: The disrupted fatty acid metabolism in hiPSC-CMs from patients with SV HF provides new insight into the pathogenesis of this disease and may help to develop novel metabolic biomarkers that may be useful for identifying pediatric patients at an earlier stage of SV HF.
Abstract 14868: Identification of Novel Small Molecule Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase II Delta for Treatment of Beta-Blocker Resistant Arrhythmia
Authors: Howard Schulman, Bheema Paraselli, Patricia Pellicena, Daniel E Levy
Journal: Circulation (2022)

Introduction. CaMKIId is a validated drug target in atrial fibrillation (AF), ventricular arrhythmia, and HF. As a key mediator of Ca 2+ action, it is hyperactivated by dysregulated Ca 2+ homeostasis with pathological consequences, which can be normalized by a variety of genetic and pharmacological manipulations. Objectives. Develop an ATP competitive CaMKIId inhibitor with nanomolar potency for initial efficacy in an AF mouse model and further optimization of selectivity, PK and low CNS penetration. Methods and Results. Molecular modeling using the crystal structure of human CaMKIId with several scaffolds as a starting point, led to development of a consistent structure activity relationship model and design of AS283. The molecule is an ATP competitive inhibitor with an IC 50 of 6nM and Ki of 1nM. Unlike KN-93, a common tool inhibitor of CaMKII in preclinical studies, AS283 inhibits the autophosphorylated, Ca 2+ -independent form of the kinase. AS283 shows preclinical proof of concept in both ventricular arrhythmia and AF models, with the latter described here. Mice with a gain of function mutation in the RyR2 receptor (R 178Q/+ ) do not undergo spontaneous AF but have an increased vulnerability to AF in response to atrial pacing. Intracardial electrophysiology with recording of atrial and ventricular electrograms (Na Li and Xander Wehrens, Baylor College) were used to select mutant and wild-type mice that exhibited AF in pacing trials. AF-positive animals were randomly assigned to treatment with placebo or AS283, with KN-93 as control. AS283 completely suppressed incidence of AF in comparison to placebo and exhibited a dose response. Autophosphorylation of CaMKIId at Thr287 was used as a biomarker of target engagement. As anticipated, atrial pacing increases intracellular Ca 2+ leading to activation of CaMKII and increased P-Thr287. AS283 blocked the increase in P-Thr287. Conclusion. AS283 is a novel, potent CaMKIId inhibitor with robust preclinical efficacy, supporting its further optimization for PK and low CNS penetration. Consistent with studies using genetic and pharmacological tools, an optimized, small molecule inhibitor of CaMKII has a promise in treating arrhythmias that are sub-optimally managed with or contraindicated to beta blockers.
Abstract 15363: Safety of Leadless Pacemakers vs. Transvenous Pacemakers in Patients Older Than 65 Years
Authors: Jorge Romero, Daniel Rodriguez, Juan C Diaz, Isabella Alviz, Magued Haroun, Cesar Nino, Mauricio Duque, Oriana Bastidas, Maria Gamero, Luis Cerna, Mohamed Gabr, Alejandro Velasco, Jose Matias, KARTIKEYA P DAVE, Domenico G Della Rocca, Sanghamitra Mohanty, Andrea Natale, Luigi Di Biase
Journal: Circulation (2022)

Introduction: Leadless pacemakers (LP) are a less invasive option compared to conventional transvenous pacemakers (TVP). They were introduced with the hope of eliminating complications associated with TVP and leads, which are more common among the elderly population. However, evidence supporting their use is uncertain. This study aims to compare the safety of the LP compared to TVP in patients 65 and older. Methods: We retrospectively analyzed consecutive patients, aged 65 and older, who were implanted a LP or TVP between August 2017 and November 2021, in 2 experienced Cardiovascular centers. The primary endpoint was a composite of any procedure-related complication (hematoma, venous thrombosis, infections, hemothorax, device dislodgement, pneumothorax). The secondary endpoint was the need for reinterventions. Results: A total of 313 patients were included; 219 received a TVP and 94 patients received a LP. Of the TVPs implanted, 68% used cephalic access, 21% axillary and 11% subclavian. The mean age was 78.9 + 7.76 for the TVP group and 82.6 +8.83 for the LP group. A total of 23 patients in the TVP group reached the primary end point vs 4 patients in the LP group, with a relative risk reduction of 60% of procedure related complications in LP compared to TVP (risk ratio [RR]:0.4; 95% CI (0.144-1.139); P= 0.043). In addition, 8 patients in the TVP group reached the secondary outcome vs none in the LP group (3.65% vs. 0%; p= &lt;0.00001).. There were no statistically significant differences in individual outcomes between the TVP group and the LP group: incision-site hematomas (11 (5%) vs. 2 (2.1%); p=0.24), venous thrombosis (2 (2%) vs 1 (0.5 %); p=0.9), infections (1 (0.5%) vs 1 (1%) ; p=0.54), hemothorax (1 (0.5%) vs. 0 (0%); p=1), device dislodgement (8 (3.6%) vs 0 (0%); p=0.11), pneumothorax (none in either group). Conclusion: This study demonstrates that LP is a safer option than TVP among patients aged 65 and older. Additional studies are needed to further establish these findings. 1
Abstract 14673: The Effect of Increasing the Ultrasound Pulse Length on Sonoreperfusion Therapy
Authors: Francois T.H. Yu, Muhammad Wahab Amjad, Soheb Anwar Mohammed, Gary Yu, Xucai Chen, John Pacella
Journal: Circulation (2022)

Background: In recent years, long and short pulse ultrasound (US)-targeted microbubble cavitation (UTMC) has been shown to increase perfusion in healthy and ischemic skeletal muscle, in pre-clinical animal models of microvascular obstruction, and in the myocardium of patients presenting with acute myocardial infarction, and microvascular vasodilation played an important role in its efficacy. Our prior preliminary data suggested that long pulse US confers enhanced sonoreperfusion efficacy compared to short pulse US. Objective: In this study, we sought to definitively compare acoustic energy matched, long (5000 cycles) and short pulse (500 х 10 cycles, separated by 100 μs intervals) US (pressure of 1.5 MPa with an equivalent total number of acoustical cycles and at the same frequency (1 MHz)), in a rodent hindlimb model, with and without microvascular obstruction (MVO). Results: By quantifying perfusion using burst replenishment contrast enhanced US imaging, we found that: (1) long and short pulses result in different vasodilation kinetics in an intact hindlimb model. The long pulse causes an initial reduction in flow due to microvascular spasm that spontaneously resolved at 4-min, followed by sustained higher flow rates (~2-folds) compared to baseline, starting 10 min after therapy ( p &lt;0.05). The short pulse caused a short-lived ~2-fold increase in flow rate that peaked at 4-min ( p &lt;0.05), but without the initial microvascular spasm; (2) the sustained increase in perfusion during long pulse is not simply reactive hyperemia; and (3) both pulses are effective in reperfusion of MVO in our hindlimb model by restoring blood volume, but only the long pulse caused an increase in flow rate after treatment 2, compared to MVO ( p &lt;0.05). Histological analysis post UTMC with either pulse configuration indicates no evidence of tissue damage or hemorrhage. Conclusions: Our findings demonstrate that the microbubble oscillation induces vasodilation and therapeutic efficacy for the treatment of MVO can be tuned by varying pulse length; relative to short pulse US, longer pulses drive greater microbubble cavitation and more rapid microvascular flow rate restoration after MVO, warranting further optimization of the pulse length for sonoreperfusion therapy.
Abstract 14627: Angiotensin-Neprilysin Inhibition in Cardiac Sarcoidosis
Authors: Raheel Ahmed, Rui Shi, Abdul Qadeer, Gerald Ballo, Joseph Okafor, Alessia Azzu, Dudley Pennell, John Baksi, Kshama Wechalekar, Athol Wells, Rajdeep Khattar, Peter Collins, Vasilis Kouranos, Rakesh Sharma
Journal: Circulation (2022)

Introduction: Sacubitril/Valsartan is an established treatment for heart failure patients with reduced ejection fraction (HFrEF). However, there is a paucity of data on its use in patients with cardiac sarcoidosis (CS). Hypothesis To establish the beneficial role of Sacubitril/Valsartan in cardiac sarcoidosis. Methods All consecutive CS patients taking Sacubitril/Valsartan were identified from our database from 2016 to 2022. They were followed up for at least 6 months with serial echocardiography. Data regarding symptoms and echocardiographic parameters were compared using Wilcoxon signed rank test. Results A total of 30 CS patients taking Sacubitril/Valsartan were identified (mean age: 56.73±11.63 years old). The diagnosis of CS was determined in all patients by a multi-disciplinary team. Patients were male predominant (73.3%). The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 20%, 10%, 10% and 3.3% respectively. Beta-blockers, mineralocorticoid receptor antagonists, prednisolone, implantable cardioverter defibrillator and cardiac resynchronisation therapy (defibrillator) were present in 93.3%, 96.7%, 53.3%, 16.7% and 56.7% patients respectively. At the time of diagnosis, 24 (80%) patients were found to have active cardiac sarcoidosis on cardiac PET. At 6-months following the commencement of Sacubitril/Valsartan, there was a significant improvement in LV ejection fraction (38.77±10.26% vs 32.87±9.30%, p&lt;0.001), LV end-systolic diameter (4.89±1.06cm vs 5.14±1.07cm, p=0.013) and New York Heart Association class (1.6±0.55 vs 2.0±0.52, p=0.001). During the median follow up of 24.9 months, the composite end-point of death and cardiac transplantation was reached in 3 (10%) patients (3 deaths and 0 cardiac transplantation). The patients experiencing at least one sustained ventricular arrhythmia (or aborted sudden cardiac death) decreased from 9 to 7 (p=0.21), the mean prednisolone dose was also comparable (11.56±4.42 vs 10.28±3.71, p=0.50) and none of the patients stopped Sacubitril/Valsartan. Conclusions Sacubitril/Valsartan in cardiac sarcoidosis patients with HFrEF is associated with at least short-term improvements in LV remodelling and functional status.
Abstract 14460: Aortic Valve Infective Endocarditis Complicated by Complete Heart Block and Gerbode’s Defect
Authors: Soban Ahmad, Dishita Pandya, Sivakumar Ardhanari
Journal: Circulation (2022)

Introduction: Aortic root abscess with complete heart block is a rare complication of infective endocarditis (IE). Early diagnosis and prompt surgical management are necessary to prevent fatal outcomes. Case Presentation: A 45-year-old male with past medical history of uncontrolled diabetes mellitus was referred to our cardiac intensive care unit for management of complete heart block. His symptoms including exertional dyspnea, hiccups, and dry cough started two weeks prior to presentation. The patient was bradycardic, hypoxic, and hypotensive on examination. Labs were significant for marked leukocytosis 21,000/ul with a neutrophilic predominance. Blood cultures were obtained, and the patient was started on empiric antibiotics vancomycin and piperacillin-tazobactam. Electrocardiogram (ECG) showed evidence of complete heart block and a temporary transvenous pacemaker was placed. A transthoracic echocardiogram was obtained that showed evidence of severe aortic regurgitation and aortic valve vegetations. Due to high clinical suspicion, a transesophageal echocardiogram was immediately performed that revealed aortic root abscess. Patient underwent successful debridement of aortic valve vegetations and aortic valve replacement. Intraoperative findings also included a subaortic left ventricular to right atrial (LV-RA) shunt also known as Gerbode’s defect that was repaired with pericardial patch. Blood cultures and intraoperative tissue cultures confirmed a Staphylococcus lugdunensis infection. He received six weeks of intravenous antibiotics. At 2-month follow-up, the patient reported doing well. Conclusion: New complete heart block may be a manifestation of aortic root abscess. This case illustrates the need to maintain a high level of suspicion for complicated infective endocarditis in patients with sepsis and complete heart block. Timely diagnosis with imaging and early surgical repair results in favorable outcomes.
Abstract 14591: Incidence of High-Risk Patients After Percutaneous Coronary Intervention for Coronary Stent Thrombosis Without Neointima Formation on Coronary Artery Stent Evaluated by Coronary Angioscopy and With High Whole Blood Platelet Aggregation
Authors: Nobusada Funabashi, Shin Akaza, Kazuo Misumi
Journal: Circulation (2022)

Introduction: The risk of coronary thrombosis after percutaneous coronary intervention (PCI) is high in the absence of neointima formation on coronary artery stents, evaluated by coronary angioscopy, and high whole blood platelet aggregation. Hypothesis: For high risk patients, despite dual antiplatelet therapy, coronary angioscopy should be used to check for neointima formation and/or whole platelet aggregation measured. Methods: This is a retrospective analysis of 2757 stents from 2757 patients (2024 male, mean 71±10 years) who underwent coronary angioscopy (timing determined by physicians) 3-12 months after PCI. The whole blood platelet aggregatory threshold index (PATI; WBA-Neo, ISK, Osaka, Japan) was calculated. For coronary angioscopy, we categorized neointima formation on stents: Grade 0) no neointima; 1) strut surrounded by neointima but not completely buried; 2) strut completely buried by neointima but still observable through neointima; 3) strut completely buried by neointima and not observable. PATI (μM) measured the minimum concentration of adenosine 5'-diphosphate causing non-reversible platelet aggregation and indicated platelet aggregation (range 0-8). The higher the PATI, the lower the platelet aggregation. Results: On coronary angioscopy, 689, 1341, 543, and 144 stents were Grade 0, 1, 2, and 3, respectively. The 689 stents in Grade 0 from 689 patients consisted of 207 (of 824=25%) Xience, 189 (of 579=33%) Combo, 117 (of 583=20%) Synergy, 91 (of 382=24%) Ultimaster, 26 (of 118=22%) BMX-J, 23 (of 94=24%) Orsiro, 18 (of 108=17%) Resolute, 3/10 (30%) NOBORI, and 1/6 MULTI LINK8 stents. Of 689 patients with Grade 0 stents, 14 had PATI &lt;2 (high platelet aggregation); eight 2-2.99; 29 3-3.99; nine PATI ranged 4-4.99; 10 5-5.99; 13 6-6.99; 17 7-7.99; and 589 &gt;8.00 (low platelet aggregation). Of 14 patients with Grade 0 stents and PATI&lt;2, two underwent single and 12 double antiplatelet drug therapies. Conclusions: 14 of 2757 patients (0.5%) simultaneously showed Grade 0 stents on coronary angioscopy and PATI &lt;2; we speculated such patients required additional antiplatelet drug therapy. The incidence of such high-risk patients after PCI was very low. Whole platelet aggregation should be checked despite dual antiplatelet therapy results.
Abstract 192: The Role Of Serum Vitamin E As A Biomarkers For Traumatic Brain Injury: Multi-center Prospective Cohort Study
Authors: Gwan J Park, Sunjin Song, Solki Kim, Jungju Lee, Youngmin Kim, HYunseok Chai, Sangchul Kim
Journal: Circulation (2022)

Background: Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for the treatment of TBI, has not been sufficiently evaluated for predicting the long-term prognosis after TBI. This study aimed to evaluate the prognostic value of vitamin E on clinical outcomes of TBI patients. Methods: A multi-center prospective cohort study was conducted in 5 university hospitals between 2018 and 2020 in Korea. All adult patients who were under 65 years of age and who visited the ED using an ambulance for head trauma were eligible. Primary and secondary outcomes were poor neurological outcome (Glasgow outcome scale (GOS) 1-4) and 1-month mortality after hospital discharge. We calculated the adjusted odds ratios (AORs) of the vitamin E for related outcomes adjusting for potential confounders. Results: Among 237 eligible TBI patients, 75 (31.6%) were classified into the poor neurological outcome group. Vitamin E level below the reference range was more observed in the poor neurological outcome group (p-value 0.04). In a univariate analysis, vitamin E depletion group showed significant higher 1-month mortality (ORs (95% CI): 5.52 (1.09-27.93)). However, there was no benefit in 1-month mortality after adjusting for confounders (adjusted ORs (95% CI): 1.57 (0.20-12.27)). And there was no significant difference in 1-month GOS between the two groups (ORs (95% CI): 2.75 (0.79-9.52)). Conclusion: Low level of serum vitamin E at ED arrival was associated with poor neurological outcome following TBI. There was only a benefit in 1-month mortality in a univariate analysis and no significant difference in 1-month mortality and 1-month GOS after adjusting for confounders.
Abstract 14906: Impact of Time Between Stacked Lesions During Radiofrequency Atrial Ablation With Active Esophageal Cooling
Authors: Marcela Mercado Montoya, Tatiana Gomez-Bustamante, Enrique Berjano, Erik B Kulstad, Steven R Mickelsen, Pablo Hernandez-Arango, Jay Schieber, James D Daniels
Journal: Circulation (2022)

Background: Active esophageal cooling during radiofrequency (RF) ablation of the left atrium (LA) has been shown to reduce esophageal injury. Although no atrioesophageal fistula has been reported in over 12 thousand uses to date, the first pericardio-esophageal fistula to occur despite cooling reinforces the fact that a threshold may exist at which heat extraction capacity may be surpassed. We aimed to examine this threshold by measuring the transmurality of esophageal injury after sequential lesion placement. Hypothesis: Reduced rest time between stacked lesions increases tissue lesion depth by enhancing thermal latency effects. Methods: Using a computational model of the left atrium, we determined esophageal lesion depth between sequentially placed RF lesions using high-power, short duration power settings (50 W for 10 s). Lesion depth was determined via Arrhenius equation, and anatomical dimensions were:1.5 mm for atrial myocardium, 0.75 mm for pericardial tissue, and 2 mm for the esophagus. Three lesions were placed on the myocardium with either 5 s or 10 s pauses in between. Final lesion transmurality was measured 45 s after the last placement to fully account for latent heating. Results: Active esophageal cooling reduced esophageal lesion transmurality by 80% after the first lesion. Sequential lesions increased esophageal lesion transmurality, with thermal latency contributing to increased lesion depth even after cessation of RF energy. Shorter timing between lesions allowed further growth in transmurality: 4% for 90 W, and 8.5% for 50 W power settings (Figure 1), showing that the efficacy of cooling against thermal latency effects decreased with the placement of each subsequent lesion. Conclusions: Active esophageal cooling reduces esophageal lesion transmurality by 80% when single lesions are placed. Stacking additional lesions at the same point reduces this safety benefit, with shorter intervals between lesions resulting in less protective effect.